Surfactant Protein A (SP-A)-mediated Clearance of Staphylococcus aureus Involves Binding of SP-A to the Staphylococcal Adhesin Eap and the Macrophage Receptors SP-A Receptor 210 and Scavenger Receptor Class A

• Published in: The Journal of biological chemistry Vol. 286; no. 6; pp. 4854 - 4870
• Main Authors: Sever-Chroneos, Zvjezdana, Krupa, Agnieszka, Davis, Jeremy, Hasan, Misbah, Yang, Ching-Hui, Szeliga, Jacek, Herrmann, Mathias, Hussain, Muzafar, Geisbrecht, Brian V., Kobzik, Lester, Chroneos, Zissis C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.02.2011; American Society for Biochemistry and Molecular Biology
• Subjects: Adhesins, Bacterial - genetics; Adhesins, Bacterial - metabolism; Animals; Chlorocebus aethiops; COS Cells; Humans; Immunology; Inflammation; Innate Immunity; Lung; Lung - metabolism; Macrophage; Macrophages, Alveolar - metabolism; Macrophages, Peritoneal - metabolism; Mice; Mice, Knockout; Phagocytosis - physiology; Pneumonia, Staphylococcal - genetics; Pneumonia, Staphylococcal - metabolism; Pulmonary Surfactant; Pulmonary Surfactant-Associated Protein A - genetics; Pulmonary Surfactant-Associated Protein A - metabolism; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Staphylococcus aureus; Staphylococcus aureus - genetics; Staphylococcus aureus - metabolism; Inflammation; Lung; Pulmonary Surfactant; Innate Immunity; Macrophage
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M110.125567

Staphylococcus aureus causes life-threatening pneumonia in hospitals and deadly superinfection during viral influenza. The current study investigated the role of surfactant protein A (SP-A) in opsonization and clearance of S. aureus. Previous studies showed that SP-A mediates phagocytosis via the SP-A receptor 210 (SP-R210). Here, we show that SP-R210 mediates binding and control of SP-A-opsonized S. aureus by macrophages. We determined that SP-A binds S. aureus through the extracellular adhesin Eap. Consequently, SP-A enhanced macrophage uptake of Eap-expressing (Eap+) but not Eap-deficient (Eap−) S. aureus. In a reciprocal fashion, SP-A failed to enhance uptake of Eap+S. aureus in peritoneal Raw264.7 macrophages with a dominant negative mutation (SP-R210(DN)) blocking surface expression of SP-R210. Accordingly, WT mice cleared infection with Eap+ but succumbed to sublethal infection with Eap- S. aureus. However, SP-R210(DN) cells compensated by increasing non-opsonic phagocytosis of Eap+S. aureus via the scavenger receptor scavenger receptor class A (SR-A), while non-opsonic uptake of Eap−S. aureus was impaired. Macrophages express two isoforms: SP-R210L and SP-R210S. The results show that WT alveolar macrophages are distinguished by expression of SP-R210L, whereas SR-A−/− alveolar macrophages are deficient in SP-R210L expressing only SP-R210S. Accordingly, SR-A−/− mice were highly susceptible to both Eap+ and Eap−S. aureus. The lungs of susceptible mice generated abnormal inflammatory responses that were associated with impaired killing and persistence of S. aureus infection in the lung. In conclusion, alveolar macrophage SP-R210L mediates recognition and killing of SP-A-opsonized S. aureus in vivo, coordinating inflammatory responses and resolution of S. aureus pneumonia through interaction with SR-A.